Edward D. Gorham’s research while affiliated with Naval Aerospace Medical Research Laboratory and other places

Objectives The objective of this study was to determine the extent to which diets with a higher inflammatory potential, as measured by the Dietary Inflammatory Index (DII), are associated with cancer development in a cohort of rural post-menopausal women. Methods This study was a secondary analysis of participants of a randomized control trial evaluating the effect of vitamin D and calcium supplementation on cancer development in rural, post-menopausal women in Nebraska. From this cohort, diets were evaluated via a 2005 Block Food Frequency Questionnaire (FFQ) at baseline and four years later (Visit 9). DII scores were calculated at both time points for each participant, including an unadjusted and energy-adjusted DII score. The relationship with DII scores and cancer development were evaluated using a chi-squared test and logistic regression, controlling for pertinent confounders. The difference in DII scores at baseline and Visit 9 for participants who developed cancer and non-cancer participants was examined via a repeated measure ANOVA test. Results There were 1977 participants with baseline and Visit 9 DII scores available for analysis. There was a significant difference in DII scores between baseline and Visit 9, with a significantly larger change in DII scores in the participants who developed cancer (p = 0.0194), shifting to higher pro-inflammatory scores at Visit 9. Cancer status was not associated with baseline DII scores, nor was DII score a predictor of cancer status, when controlling for confounders. Conclusions These findings illustrate how dietary patterns in persons diagnosed with cancer had significant changes over time, increasing inflammatory diet potential. This increase in inflammatory potential in cancer patients may impact outcomes like treatment success, overall survival, and cancer recurrence, creating a need for more research to further analyze the impact of cancer diagnoses on diet changes, and if these changes are detrimental to cancer survivor outcomes. Funding Sources None.

This abstract was not presented at the conference. Citation Format: McDonnell SL, Baggerly CA, French CB, Baggerly LL, Garland CF, Gorham ED, Lappe JM. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-10-02.

[This corrects the article DOI: 10.1371/journal.pone.0152441.].

Background While numerous epidemiologic studies have found an association between higher serum 25-hydroxyvitamin D [25(OH)D] concentrations and lower breast cancer risk, few have assessed this association for concentrations >40 ng/ml. Objective To investigate the relationship between 25(OH)D concentration and breast cancer risk across a broad range of 25(OH)D concentrations among women aged 55 years and older. Methods Analyses used pooled data from two randomized clinical trials (N = 1129, N = 2196) and a prospective cohort (N = 1713) to examine a broad range of 25(OH)D concentrations. The outcome was diagnosis of breast cancer during the observation periods (median: 4.0 years). Three analyses were conducted: 1) Incidence rates were compared according to 25(OH)D concentration from <20 to ≥60 ng/ml (<50 to ≥150 nmol/L), 2) Kaplan-Meier plots were developed and 3) multivariate Cox regression was used to examine the association between 25(OH)D and breast cancer risk using multiple 25(OH)D measurements. Results Within the pooled cohort (N = 5038), 77 women were diagnosed with breast cancer (age-adjusted incidence: 512 cases per 100,000 person-years). Results were similar for the three analyses. First, comparing incidence rates, there was an 82% lower incidence rate of breast cancer for women with 25(OH)D concentrations ≥60 vs <20 ng/ml (Rate Ratio = 0.18, P = 0.006). Second, Kaplan-Meier curves for concentrations of <20, 20–39, 40–59 and ≥60 ng/ml were significantly different (P = 0.02), with the highest proportion breast cancer-free in the ≥60 ng/ml group (99.3%) and the lowest proportion breast cancer-free in the <20 ng/ml group (96.8%). The proportion with breast cancer was 78% lower for ≥60 vs <20 ng/ml (P = 0.02). Third, multivariate Cox regression revealed that women with 25(OH)D concentrations ≥60 ng/ml had an 80% lower risk of breast cancer than women with concentrations <20 ng/ml (HR = 0.20, P = 0.03), adjusting for age, BMI, smoking status, calcium supplement intake, and study of origin. Conclusions Higher 25(OH)D concentrations were associated with a dose-response decrease in breast cancer risk with concentrations ≥60 ng/ml being most protective.

Flowchart of participants. (TIFF)

Background It has been reported that higher plasma 25-hydroxyvitamin D is associated with lower risk of type 2 diabetes. However the results to date have been mixed and no adequate data based on a cohort are available for the high end of the normal range, above approximately 32 ng/ml or 80 nmol/L. Methods We performed a cohort study of 903 adults who were known to be free of diabetes or pre-diabetes during a 1997–1999 visit to a NIH Lipid Research Centers clinic. Plasma 25(OH)D was measured at Visit 8 in 1977–1979. The mean age was 74 years. The visit also included fasting plasma glucose and oral glucose tolerance testing. Follow-up continued through 2009. Results There were 47 cases of diabetes and 337 cases of pre-diabetes. Higher 25(OH)D concentrations (> 30 ng/ml) were associated with lower hazard ratios (HR) for diabetes: 30–39 ng/ml or 75–98 nmol/L: HR = 0.31, 95% CI = 0.14–0.70; for 40–49 ng/ml or 100–122 nmol/L: HR = 0.29, CI = 0.12–0.68; for > 50 ng/ml or 125 nmol/L: HR = 0.19, CI = 0.06–0.56. All HRs are compared to < 30 ng/ml or 75 nmol/L. There was an inverse dose-response gradient between 25(OH)D concentration and risk of diabetes with a p for trend of 0.005. Each 10 ng/mL or 25 nmol/L higher 25(OH)D concentration was associated with a HR of 0.64, CI = 0.48–0.86. 25(OH)D concentrations were more weakly inversely associated with pre-diabetes risk, and the trend was not significant. Conclusion Further research is needed on whether high 25(OH)D might prevent type 2 diabetes or transition of prediabetes to diabetes.

In Reply Ms Jaroudi and Dr Peiris suggest that the length of follow-up in our study may have been insufficient to detect a change in cancer incidence. We agree that longer follow-up would have been desirable, but we were limited by funding. However, mechanisms proposed for potential anticancer effects include signaling that may result in short-term effects.¹,2